1. Field of the Invention
The present invention relates to a method and apparatus for treating obesity, and more specifically the invention relates to an artificial gastric valve that can be implanted in a patient for treating obesity.
2. Description of the Related Art
In the opinion of many health care experts, obesity is the largest health problem facing westernized societies and is considered an epidemic. From a medical standpoint, obesity is the primary risk factor for type 2 diabetes and obstructive sleep apnea. It increases the chances for heart disease, pulmonary disease, infertility, osteoarthritis, cholecystitis and several major cancers, including breast and colon. People with Body Mass Index (“BMI”) greater than 40 are considered morbidly obese. People with BMI between 30 and 40 are considered obese. Most importantly, high BMI has been shown to cause a reduction in life expectancy.
From an economic standpoint, it is estimated that more than 100 billion dollars are spent on obesity and treating its major co-morbidities. This does not even consider the psychological and social costs of this epidemic problem. Despite these alarming facts, treatment options for obesity remain limited. The desire to eat and the body's counter regulatory system when caloric intake is reduced, makes the treatment of obesity quite a difficult task.
The obesity epidemic and its medical impact have been well documented. Currently over 50 billion dollars are spent on over the counter weight loss products and programs. The number of invasive surgical procedures such as gastric bypass and lap band being performed for severe obesity is rapidly increasing. In the past 5 years there has been a 450% increase in surgical procedures for obesity. On average these procedures cost more than $25,000. Furthermore, the complicated nature of these procedures and potential for negative long term effects make only the most obese candidates for these procedures. Despite the efficacy of current surgical procedures, there is a large opportunity to vastly improve their effectiveness and limit their complications. It is only in the last several years, that a majority of health care providers viewed obesity as a disease that justified invasive and aggressive management. The data for the negative impact of obesity on health is now overwhelming. Current procedures are merely first generation approaches and have not made an overall impact on obesity treatment and prevention. Consequently, there is a large market opportunity for medical devices that better understand the pathophysiology of obesity.
With over 60% of the United States Population obese or overweight, market size is limited only by the development of safe and effective technology. Currently, 150,000 bariatric cases are performed in the US. Approximately, 30,000 are lap bands. At present, staplers and medical devices for obesity are approximately a 500, million dollar market. This does not include the 50 billion dollars spent on weight loss products and programs. Nor does it include the estimated 100 billion dollar cost treating the complications of obesity. With the large discrepancy between need and effective treatments, most analysts believe that the obesity market could rival the cardiac stent market if proper devices are developed. The devices developed to date all have issues.
Gastric Bypass
Gastric Bypass is the most common surgical procedure performed to treat morbid obesity. The procedure involves using a stapler that cuts and divides tissue. This is used to produce a pouch that serves as a smaller stomach. This pouch is attached to a limb of divided intestine. Finally, intestinal continuity is restored by attaching the intestine to the intestine.
Numerous things happen when a gastric bypass is performed. The new stomach is smaller and holds less food. Food goes directly into the small intestine, bypassing the bottom portion of the stomach and the initial area of the intestine. Food does not mix with the digestive juices from the liver and pancreas until a large portion of the GI tract has been passed. As a result, the operation makes people eat less and causes impaired absorption of food, minerals and vitamins.
While effective, the bypass can cause numerous long term issues. There is a real mortality rate associated with the procedure. Poor iron absorption can cause anemia. Poor calcium absorption could cause osteopenia. Poor vitamin absorption can cause deficiency in Vitamin A, 0, or thiamine. Additionally, there is a risk of marginal ulcer, stricture, and other morbidity.
For these reasons, the number of patients seeking gastric bypass appears to have stabilized. For the last five years, growth has been exponential. Currently, patients are searching for the efficacy of bypass without the potential complications.
Besides the standard gastric bypass, there are other procedures that are similar. They include banded bypass, bilio-pancreatic diversion with duodenal switch and Scopinaro procedure. All combine some gastric alteration with an intestinal bypass. All offer weight loss. But all have a short and long term complication profile that preclude them from being considered ideal treatments.
Presently, all these procedures can be performed laparoscopically. While this offers faster recovery, reduced pain, and lower risk of hernia formation, it does not eliminate the short and long term complications associated with gastric bypass.
Laparoscopic Adjustable Gastric Banding
The purpose of the gastric band is to create a narrowing in the proximal stomach that functions as a valve. The valve reduces the space available for food in the stomach and delays the emptying of the stomach. This hopefully makes people eat less and want to eat less frequently. The band can be tightened with the insertion of liquid through a port that is placed beneath the skin. New generations will offer band inflation without an invasive needle stick. However, the outlet would still remain fixed and the band would still represent a high pressure zone.
The attraction of the band includes its low peri-operative morbidity and mortality. Since there is no alteration of the GI tract itself, recovery is rapid. However the fixed high pressure zone leads to numerous issues.
Certain patients never achieve an acceptable level of weight loss. When the band is tightened to enhance effect, there can be dilation of the pouch above the band and the esophagus. Patients complain of regurgitation and dysphagia. Also the high pressure that is transmitted proximally causes a stomach that is more resistant to distension and the forces caused by food bolus.
Several companies are expected to enter the LAGB market. Ethicon Inc, a division of Johnson and Johnson is expecting approval of there obtech band in 2007. Additionally they have accumulated IP that involves improved design including self adjustment. Other band companies in Europe include Mid-Band and Helioscope. A new entry is Endo-Art which offers an improved method of non invasive band adjustment.
Gastric Balloons
A simple concept to reduce food intake is the placement of a space occupying balloon. These are inserted with the help of an endoscope. The balloon is inflated to 600 to 850 cc. This occupies a large portion of space in the stomach and leads to early satiety.
There are numerous issues that have limited the clinical usefulness of balloons. The harsh acidic environment of the stomach can cause destruction of the balloon. As a result, the balloon needs to be replaced every six months. More importantly, the large balloon causes the stomach to reset. Since there is no external restriction the stomach can dilate. In fact the stomach can dilate to quite extreme levels. As the volume of a sphere changes with the radius to the third power, even a small level of dilatation can lead to an impressive increase in the size of the gastric reservoir.
As a result, most view balloons as a bridge for very high risk patients, to more efficacious treatment modalities, such as gastric bypass. Old version of the balloon such as the Taylor or Guerin balloons were recalled from the market. Bioenterics, the maker of the lap band has re-introduced the Bioenterics intragastric balloon, with their improved silicone.
Gastric Pacing
There are several investigational designs that have explored using electrical stimulation with the use of a pacemaker to either the gastric tract or essential nerves. The most investigated is trans gastric pacing utilized by Transneuronix, which was recently purchased by Medtronics, for a minimal value of 260 million dollars. With incentives, the deal could be worth one billion dollars.
This approach involves the insertion of electrical leads on the lesser curvature of the stomach, close to the fibers of the vagus nerve. These leads are attached to a pacemaker.
There are numerous theories regarding the effect of gastric pacing. The original hypothesis was that the pacing interfered with the normal electrical system of the stomach and caused a delay in gastric emptying. This delay would allow the stomach to stay full and reduce food ingestion. Unfortunately, gastric emptying studies failed to show consistent delay in gastric emptying. More recent theories involve stimulation of enteric nerves, and local hormonal factors.
Several large trials that have included sham arms have investigated the efficacy of gastric pacing. To date, they have not shown consistent efficacy. Recently, Medtronic announced that the most recent trial failed to demonstrate weight loss.
Another version using similar technology is being employed by Impulse Dynamics which is a privately held Israeli based. In their system, impedance is measured and the gastric pacing is linked to a change in impedance. Clinical trials are being done in Vienna and the USA.
Cyberonics Inc. has investigated the use of vagus nerve stimulation for obesity. Favorable animal data lead to a six patient clinical pilot. Results were similar to what was reported by Transneuronix. Two patients did well, two had limited efficacy and two had no effect at all. The conclusion was that there was a real effect, but that more investigation was needed to master the needed signal.
Leptos, a new start up is investigating the use of splanchnic nerve stimulation. Similar to the vagus nerve, the splanchnic nerve is a conduit for information from the stomach and intestines to the brain. Promising animal data has been generated and pilot human trials are planned. Leptos has completed a second round of financing at a valuation of 12 million dollars.
Perhaps the most futuristic approach is being developed by Intrapace. Their approach is to design an internally placed pacemaker that is inserted through a trans-oral approach. In addition to all the unknowns that the other stimulation products have, this approach adds new dimensions. They include the need for a small or rechargeable battery, limited space, the harsh gastric environment and the difficulty in generating the high power signal believed necessary to stimulate small C fibers.
All pacing concepts are based on stimulating the intrinsic wiring of the stomach and mimic what happens when the stomach is stimulated by the ingestion of food. The problem is that while we know that this wiring exists, we do not know the Morse code needed to decipher. The pacers generate an electrical signal that goes on or off. There is no crescendo or decrescendo response. Only Impulse Dynamics tries to overcome this obstacle. Additionally, there is no physiologic response to titrate the response. Thus only expensive clinical trials can be performed to see if the pacing is effective. The Transneuronix experience highlights these issues.
Many patients lost weight in their clinical trial. However, when compared to placebo the response was not statistically Significant. Other, than repeat an entire trial with different pacing parameters or a patient selection, there is little that can be done. Basically, improved parameters will need to be guessed and only a lengthy trial will determine whether effective.
Pacing strategies are attractive since they would be low risk procedures. However, they will be expensive and efficacy may prove difficult. Contrary to cardiac pacemakers, there is no short term way of determining whether you have achieved your clinical objective. As a result, improvements will be difficult to prove.
Other hurdles besides clinical approval, will be gaining reimbursement. These devices will be expensive and require battery change at regular intervals. Even if FDA requirements for pre-market approval are met, it will be a long time before reimbursement is obtained from a majority of commercial insurance plans. Furthermore, approval for Medicare reimbursement will be difficult. The expense of these devices and the cost of invasive implant and the need for battery change will reduce the number of potential self or cash pay recipients.
Endoscopic or Trans Oral Restriction or Sleeves
Trans-oral approaches offer the potential to have access to the GI tract without incision. Theoretically, procedures could be done in an outpatient setting without general anesthesia or endotracheal intubation. These approaches could limit morbidity and make the development of sepsis, wound breakdown and fistula less likely. Finally, the potential reduced cost of outpatient procedures could make treatment more affordable.
There is an extensive list of trans-oral approaches that are being developed. These include oral devices, bezoars that occupy space in the stomach, internal suturing devices, stents and grafts that serve as a conduit for food bypassing areas of caloric absorption, gastric clamping or fusion techniques, radiofrequency ablation and intra gastric pacing. At present, an oral device and a balloon that occupies space have been utilized in clinical practice. Endoscopic suturing has been done for gastric fistulas and dilated gastrojejunostomy attachments with promising early results. Suturing has also been done as a primary procedure for obesity in South America.
Oral Devices
The concept of an oral device is to occupy the space under the roof of the mouth. This forces patients to take smaller bites, eat slowly and hopefully eat smaller meals. The device, called the DDS, (Scientific Intake) is inserted by the patient prior to eating and removed at the conclusion of the meal. Each person has an impression produced and the device custom made. A recent modification allows for a chip to be inserted to check for compliance.
At present the device has been utilized by over 3000 people. There are no reports of any significant adverse events. An acute study performed at Pennington Institute revealed that the study group eat 23% less food and this was associated with a six pound weight loss. A multi-centered FDA trial was scheduled to begin in January of 2006, to objectively study the device and the compliance pattern of patients.
The future market of this device is not designed to be competitive with the companies products. This approached is being advocated as a first line and for those with minimal obesity. For success there will need to be compliance and extensive behavior modification will be combined with the oral device.
Internal Suturing and Gastric Clamping
Several approaches are being designed to reduced the size of the stomach and perform an internal restrictive obesity operation. The idea is to reduce gastric capacity similar to what is done with a vertical banded gastroplasty. Several established and startup companies are examining these 30 techniques. They are attempting to utilize either a combination of a suturing device and methods that fuse the walls of the stomach.
Satiety Inc. a privately held start up, which has an approach to internally reduce the size of the gastric reservoir. They are developing tissue fusion and suturing device to accomplish this goal. There are several major issues. First there is the technical challenge of designing an endoscopic product that fits through a currently available endoscope or overtube to perform the procedure. Furthermore, if accomplished the durability of these procedures will have to be questioned. Staple breakdown rates of 10-20% have been reported for externally applied staplers. How internal sutures or fusion techniques will hold in the acidic gastric environment, remains to be determined. Furthermore, in open procedures, unless these procedures were reinforced with synthetic bands, they had very short term efficacy. Another major question will be the regulatory path and follow up period that the FDA will find acceptable. If more than one year of follow up is required, these durability issues may prove terminal.
Gastric Sleeves
Another technique to reproduce the benefits of a gastric bypass transorally are gastric sleeves or elephant trunks. The idea is to utilize a graft, that is anchored to the GI tract by an attachment device such as a stent. The graft would be lodged into the jejunum or proximal ileum. Food would travel down the conduit, not mixing with the digestive enzymes and reduce small bowel absorption. This could potentially be combined with a gastric restrictive device to imitate a gastric bypass. Others have also proposed combining such a technique with an Adjustable Laparoscopic Gastric Band.
Numerous start up companies that have raised capital at valuations approaching 20 million dollars, have taken this approach. They include GI Dynamics, Barosense and GastroRx.
Issues with sleeves or conduit procedures include, difficulty in fixation, potential for obstruction and kinking, migration and an unknown effect on food consumption. As food is in reduced contact with intestinal mucosa, this could actually stimulate recipients to eat more to compensate.
Insertion of foreign bodies into the gastro intestinal tract is different than placing stents into the vascular system. There are strong muscular contractions called peristalsis that drives food down the intestinal tract. These forces will make these devices difficult to anchor. Thus they will migrate and kink and cause intestinal obstruction. Additionally, the graft will serve as an absorber of the transient pressure increases seen with food consumption.
These devices will have to overcome all these technical barriers. Once these are overcome, then efficacy will need to be determined. These devices have no real precedent surgical procedure to predict their long term effectiveness and durability.
Most Common Techniques
The most common operation in the United States is the Gastric Bypass. With gastric bypass many investigators have reported weight loss results that exceed 70% of excess weight. However, this efficacy does not come without complication. The accepted mortality of the procedure is 1 in 200. Even higher figures have recently been reported among beneficiaries of Medicare. Furthermore, there is an increasing recidivism rate. Weight gain of 10 to 40% of maximum weight loss has been reported. Immediately after surgery, most patients report less desire to eat. Unfortunately, 6 to 12 months after surgery the urge to eat seems to return. Most, still cannot eat the portion size they once consumed. However they replace this with eating small amounts of calorically dense foods more often. There can be expansion of the pouch and dilation of the attachment between the stomach and the intestine.
Another view, is that the operation is fixed and unlikely to work better than immediately after it was performed. As the patient challenges the procedure, the tissue changes to allow more food to enter. The negative reinforcement the operation offers decreases over time. We learn what to eat, how to eat it and sub consciously learn tricks that allow us to return to the habits that made the patient obese.
Other common techniques include the lap band or adjustable gastric bands which have similar limitations. The band is a synthetic medical device that can be thought of as a ring that goes around the first portion of the stomach. Inside the ring is an inflatable balloon. This balloon can be tightened by inflating fluid that makes the outlet of the stomach smaller.
The purpose is to make the recipient eat less food and smaller portions. While the lap band is adjustable this does not change the fact that the restriction is fixed. The lap band creates a high pressure zone that delays food intake past this point. This high pressure is transmitted to all places above the band. This can lead to dysphagia, dilatation of the stomach and esophagus above the band, regurgitation and reflux. Furthermore, the persistent high pressure would make it more difficult for a limited bolus of food to initiate satiety signals. While early, research has shown that ghrelin (a hormone that has been linked to satiety) levels stay persistently high in lap band patients. Low ghrelin levels have been reported in post bypass patients and are thought to be partially responsible for the post operative anorexia experienced by patients.
The advantages of the lap band, compared to gastric bypass are multiple. The gastrointestinal tract does not have to permanently altered. There is no malabsorption of vitamins and minerals. The operative morbidity and mortality is much lower. On the other hand, results are more variable. 10% of recipients have minimal weight loss. Secondary to poor weight loss or other symptoms caused by the fixed obstruction, the re-operative surgical rate is also approximately 10%.
As stated above, it is estimated that up to 60% of the population in the United States is obese or overweight. Of these patients, 5-6% are considered morbidly obese because they are approximately 50 kg above their ideal body weight. Treatment options include dietary modification, very low calorie liquid diet, pharmaceutical agents, counseling, exercise programs and surgery. Surgical procedures that restrict the size of the stomach and/or bypass parts of the intestine are the only remedies that provide lasting weight loss for the majority of morbidly obese individuals. Surgical procedures for morbid obesity are becoming more common based on long-term successful weight loss result. Increase awareness regarding the dangers of obesity combined with the fact that these procedures are now being done with a laparosope, in a minimally invasive manner, have made these procedures one of the fastest growing areas of surgery.
The surgeries which create malabsorption, such as the by-pass operation, although effective in weight reduction, involve permanent modification of the GI tract and have a risk of short and long term complication and even death. A method to create restriction of food flow in the stomach involves a device called gastric band in which a band is tightened around part of the stomach. The band operation does not modify the GI tract at the time of surgery, however because the restrictive band is fixed in diameter, it can create long term complications. The fixed high pressure caused by the obstruction is transmitted to the gastro esophageal junction and esophagus. These structures are forced to accommodate this increased load. This can result in adaption of the pouch, esophageal dysfunction, and severe dysphagia. At present, only 50% of band recipients have what is considered a successful bariatric procedure. Annually 5% of patients require revision or band removal. Present day gastric bands are fixed in diameter with the ability to change the diameter via injection of liquid into a balloon. This type of diameter change involves a visit to the physician and is not dynamic. Thus people develop gastric pouch dilation, stoma obstruction, motility disturbances (pseudo achalasia), esophagitis and other symptoms related to a fixed barrier in the stomach.
This review of the obesity device field, emphasizes the need for a better surgical device for the treatment of obesity. The desired device would need to be easily placed. It would need to be reversible. It would need to make people eat less feel less hungry. It would need to be activated when it is needed, not be locked in the on position. It would need to be able to be altered to meet changing clinical needs.